A randomized (allocation according to the random principle) Phase II, 2-armed study in transplant ineligible (TI) patients with newly diagnosed multiple myeloma (NDMM) comparing Carfilzomib + Thalidomide + dexamethasone (KTd) versus Carfilzomib + Lenalidomide + dexamethasone (KRd) induction therapy with respect to response rates and investigating a Carfilzomib (K) monotherapy maintenance strategy
- Conditions
- Transplant ineligible patients with newly diagnosed multiple myelomaMedDRA version: 16.1Level: HLTClassification code 10028229Term: Multiple myelomasSystem Organ Class: 100000004851Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2016-000475-24-AT
- Lead Sponsor
- AGMT gGmbH
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 124
•Age = 18 years
•Able to provide written informed consent in accordance with federal, local, and institutional guidelines
•newly diagnosed, symptomatic multiple myeloma
•Transplant-ineligibility (age > 65 years or patients not eligible due to comorbidities determined by investigator or patients not willing to undergo ASCT on personal preference)
•Measurable disease, as defined by one or more of the following (assessed within 21 days prior to randomization):
oSerum M-protein = 0.5 g/dL, or
oUrine M-protein = 200 mg/24 hours, or
oIn subjects without detectable serum or urine M-protein, serum-free light chain (SFLC) > 100 mg/L (involved light chain) and an abnormal ?/? ratio
•No prior treatment for multiple myeloma
•Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0-1
•Patients at cardiac risk (NYHA >II or pre-existing coronary heart disease or any other relevant cardiac complication) should be scheduled for a baseline ECHO and can only be included if the LVEF is =40%); independent of cardiac risk ECG has to be done for inclusion of Asian patients and patients > 75 years of age
•Adequate organ and bone marrow function within the 21 days prior to randomization defined by:
oBilirubin < 2 times the upper limit of normal (ULN), Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) < 3 times the ULN
oabsolute neutrophil count (ANC) = 1000/mm3 (growth factor support for max 3 days allowed to achieve this value)
oHemoglobin = 7.0 g/dL (Use of erythropoietic stimulating factors and red blood cell [RBC] transfusion per institutional guidelines is allowed, however the most recent RBC transfusion may not have been done within 7 days prior to obtaining screening hemoglobin.)
oPlatelet count = 30,000/mm3
•Calculated or measured creatinine clearance (CrCl) of > 30 mL/min. Calculation should be based on the Cockcroft and Gault formula: [(140 – Age) · Mass (kg) / (72 · Creatinine mg/dL)]; multiply result by 0.85 if female
•Females of childbearing potential (FCBP) must have a confirmed negative serum pregnancy test within the 21 days prior to randomization
•Females of childbearing potential and male subjects who are sexually active with FCBP must agree to use effective concomitant method(s) of contraception during the study and for 30 days (women) and 90 days (men) following the last study drug treatment administration.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 4
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 120
•ECOG =2
•Frail patients
• Waldenström macroglobulinemia
•POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes)
•Plasma cell leukemia (> 2.0 × 109/L circulating plasma cells by standard differential)
•Myelodysplastic syndrome
•Smoldering Myelom and MGUS
•Second malignancy within the past 5 years except:
oAdequately treated basal cell or squamous cell skin cancer
oCarcinoma in situ of the cervix
oProstate cancer Gleason score = 6 with stable prostate-specific antigen (PSA over 12 months
oDuctal breast carcinoma in situ with full surgical resection (i.e., negative margins)
oTreated medullary or papillary thyroid cancer
oSimilar condition with an expectation of > 95% five-year disease-free survival
•History of or current amyloidosis
•Immunotherapy within the 21 days prior to randomization
•Glucocorticoid therapy within the 14 days prior to randomization that exceeds accumulative dose of 160 mg dexamethasone or 1000 mg prednisone
•Extended field radio therapy (more than 3 fields) within the 21 days prior to randomization
•Known history of allergy to Carfilzomib, Captisol (a cyclodextrin derivative used to solubilize carfilzomib) or any other component of formulation
•Contraindication to dexamethasone, thalidomide or lenalidomide or any of the required concomitant drugs or supportive treatments, including hypersensitivity to antiviral drugs
•Active congestive heart failure (New York Heart Association [NYHA] Class III or IV), symptomatic ischemia, conduction abnormalities uncontrolled by conventional intervention, acute diffuse infiltrative pulmonary disease, pericardial disease, or myocardial infarction within 4 months prior to enrollment
•Active infection within the 14 days prior to randomization requiring systemic antibiotics and/or antiviral therapy
•Pleural effusions requiring thoracentesis within the 14 days prior to randomization
•Ascites requiring paracentesis within the 14 days prior to randomization
•Uncontrolled hypertension or uncontrolled diabetes despite medication
•Significant neuropathy (Grade 2 with pain or Grade 3 or higher) within the 14 days prior to randomization
•Known cirrhosis
•Known human immunodeficiency virus (HIV) seropositivity or active hepatitis C or hepatitis B infection (subjects with past hepatitis B virus [HBV] infection or resolved HBV infection defined as having a negative HBsAg test and a positive antibody to hepatitis B core antigen [anti HBc] antibody test are eligible; subjects positive for hepatitis C virus [HCV] antibody are eligible only if polymerase chain reaction [PCR] is negative for HCV RNA.)
•Participation in another interventional study within the 28 days prior to randomization
•Major surgery (except kyphoplasty) within the 28 days prior to randomization
•Female subjects who are pregnant or lactating
•Any other clinically significant medical disease or social condition that, in the investigator’s opinion, may interfere with protocol adherence or a subject’s ability to give informed consent, be compliant with study procedures, or provide accurate information.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method